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Global longitudinal strain (GLS) is becoming routinely used to direct the medical management of various cardiac diseases, but its application in pregnancy is unclear. Our objective was to perform a meta-analysis and pool multiple study data to consolidate the evidence base for the role of GLS in the assessment of women with hypertensive disorders of pregnancy (HDP). Electronic database searches were performed in PubMed/Medline and EMBASE for research articles reporting GLS in pregnancies complicated by HDP and normotensive pregnancies that have been published up to September 2021. The meta-analysis included 17 studies with a pooled sample size of 1723 participants, which included 951 women with HDP, of which 680 were preeclamptic, and 772 controls. The primary random-effects pooled analysis demonstrated a statistically significant weighted mean difference in GLS between the HDP and control group (mean difference: 3.08% [CI, 2.33–3.82], P

Le malattie del trofoblasto di origine gestazionale (GTD) rappresentano una complicanza rara della gravidanza. Esse si dividono in forme benigne (mola idatiforme parziale e completa) e maligne (tumori del trofoblasto, GTN). Nonostante la prognosi favorevole che attualmente accompagna tale diagnosi, la natura stessa di queste malattie costituisce una considerevole fonte di stress per le pazienti che ne sono affette. Metodi. Trentuno pazienti affette da GTD hanno completato una batteria di questionari autosomministrati volti a valutare il ruolo dei meccanismi di difesa nell’influenzare l’adattamento psicologico alla malattia, in particolare la presenza di sintomi ansiosi e depressivi e lo stress legato all’infertilità. Risultati. Le pazienti affette da tumori del trofoblasto riportano un maggiore utilizzo di meccanismi di difesa maturi rispetto alle pazienti con mola idatiforme. Le analisi di regressione evidenziano che, al netto di variabili demografiche e mediche correlate alla patologia, i meccanismi di difesa immaturi mantengono una relazione specifica con l’ansia di stato e con lo stress legato all’infertilità riportato dalle pazienti. Conclusioni. I risultati suggeriscono l’importanza di considerare, nella progettazione di interventi clinici, gli specifici meccanismi di difesa messi in atto dalle pazienti, in quanto significativamente coinvolti nel modulare l’adattamento psicologico alle GTD Gestational Trophoblastic Disease (GTD) is a group of disorders that derive from the placenta and arise after a rare gestational event. They can be divided into pre-malignant forms (partial and complete hydatidiform mole) and malignant forms called Gestational Trophoblastic Neoplasia (GTN). Despite a favourable prognosis, the nature of this group of disorders can be a source of stress for patients who are affected by this disease. Methods. Thirty-one patients diagnosed with GTD completed a battery of self-administered questionnaires aimed at analysing the psychological adaptation of the patients to the disease. The variables analysed were the following: defense mechanisms, anxiety, depression and infertility-related stress. Results. Patients with GTN use mature defense mechanisms significantly more than patients with hydatidiform mole. Regression analyses highlight that, considering demographic and clinical variables, immature defense mechanisms are significantly related to state anxiety. Immature defence mechanisms also significantly predict infertility-related global stress. Conclusions. The results show the importance of taking into consideration defense mechanisms used by patients, as they are involved in the modulation of psychological adaptation to GTD.

Objective: Preterm birth (PTB) is more common in pregnancies conceived by in-vitro fertilization (IVF) as compared with those conceived naturally. However, the extent to which this is attributed to spontaneous labor or to iatrogenic indications has not been determined. The aim of this study was to quantify the risk of spontaneous PTB (sPTB) in singleton pregnancies resulting from IVF or intracytoplasmic sperm injection (ICSI) treatment as compared with that in spontaneously conceived pregnancies. Methods: An electronic search of PubMed/MEDLINE, Scopus and Web of Science to September 2017 and manual search of reference lists identified articles comparing the risk of sPTB in IVF/ICSI vs spontaneously conceived singleton pregnancies. Inclusion criteria were singleton conception with IVF/ICSI, PTB defined as delivery before 37 weeks' gestation and cohort design with clear distinction between spontaneous and indicated PTB. The primary outcome was sPTB < 37 weeks. Relevant secondary outcomes were also analyzed, including sPTB < 34 and < 32 weeks, preterm prelabor rupture of membranes, stillbirth, perinatal mortality, neonatal sepsis, respiratory distress syndrome and gastrointestinal morbidity. A meta-analysis provided the estimation of risk of sPTB in IVF/ICSI pregnancies. Results: In total, 674 records were identified from the search, of which 15 met the inclusion criteria and were included in the meta-analysis. A pooled crude analysis of the primary outcome generated a total sample size of 61 677 births, including 8044 singletons conceived after IVF/ICSI and 53 633 conceived spontaneously. A pooled crude data analysis showed a significant increase in the incidence of sPTB < 37 weeks in singleton IVF/ICSI pregnancies compared with those conceived spontaneously (810/8044 (10.1%) vs 2932/53 633 (5.5%); odds ratio (OR), 1.75; 95% CI, 1.50–2.03; I2= 39%). A subgroup analysis of studies matching for maternal age and parity confirmed the finding (OR, 1.63; 95% CI, 1.30–2.05; I2= 33%). A pooled crude analysis of secondary outcomes showed a significant increase in the incidence of sPTB < 34 weeks in pregnancies conceived after IVF/ICSI compared with those conceived spontaneously (37/1012 (3.6%) vs 24/1107 (2.2%); OR, 1.78; 95% CI, 1.03–3.08; I2= 6%) and did not show any significant difference for any of the other secondary outcomes analyzed. The quality of evidence, rated using the GRADE criteria, was low for the outcome sPTB < 37 weeks and very low for sPTB < 34 weeks. Conclusions: The risk of sPTB in singleton pregnancies resulting from IVF/ICSI is significantly greater than that in spontaneously conceived singletons. These findings should be interpreted with caution given the low quality of the available evidence. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Aim: The study aimed to describe prenatal diagnosis and the outcome of complete hydatidiform mole and coexistent normal fetus (CHMCF). Methods: This was a retrospective case series of 13 patients with CHMCF. Prenatal diagnosis, outcome and development of gestational trophoblastic neoplasia (GTN) were reviewed. Results: Ultrasound diagnosis was carried out in 12 of 13 cases at 17 ± 2.7 weeks of gestation (mean ± SD). Six patients showed abnormalities suggestive of subchorionic hematoma on first trimester ultrasonography (US). Prenatal invasive procedures were performed in 8 of 13 cases (62%). Two women decided to terminate their pregnancies. Four ended in late miscarriages (36%, 4 of 11) between 13 and 21 weeks, and early neonatal death occurred in 1 case (9%, 1 of 11); 5 women delivered a live baby with a mean gestational age of 31 weeks (range 26-37 weeks) with an overall neonatal survival of 45% (5 of 11). GTN occurred in 31% of cases (4 of 13). Conclusions: The first trimester US features of CHMCF are not well-documented. Our series showed that abnormalities of CHMCF could be misdiagnosed as subchorionic hematoma in the early first trimester. When CHMCF is confirmed by expert US, prenatal invasive procedures should be carefully evaluated depending on the associated US findings and exhaustive counseling should be performed.

Background Traditionally, pregnancy was considered to have a positive effect on endometriosis and its painful symptoms due not only to blockage of ovulation preventing bleeding of endometriotic tissue but also to different metabolic, hormonal, immune and angiogenesis changes related to pregnancy. However, a growing literature is emerging on the role of endometriosis in affecting the development of pregnancy and its outcomes and also on the impact of pregnancy on endometriosis. The present article aims to underline the difficulty in diagnosing endometriotic lesions during pregnancy and discuss the options for the treatment of decidualized endometriosis in relation to imaging and symptomatology; to describe all the possible acute complications of pregnancy caused by pre-existing endometriosis and evaluate potential treatments of these complications; to assess whether endometriosis affects pregnancy outcome and hypothesize mechanisms to explain the underlying relationships. Methods This systematic review is based on material searched and obtained via Pubmed and Medline between January 1950 and March 2015. Peer-reviewed, English-language journal articles examining the impact of endometriosis on pregnancy and vice versa were included in this article. Results Changes of the endometriotic lesions may occur during pregnancy caused by the modifications of the hormonal milieu, posing a clinical dilemma due to their atypical appearance. The management of these events is actually challenging as only few cases have been described and the review of available literature evidenced a lack of formal estimates of their incidence. Acute complications of endometriosis during pregnancy, such as spontaneous hemoperitoneum, bowel and ovarian complications, represent rare but life-threatening conditions that require, in most of the cases, surgical operations to be managed. Due to the unpredictability of these complications, no specific recommendation for additional interventions to the routinely monitoring of pregnancy of women with known history of endometriosis is advisable. Even if the results of the published studies are controversial, some evidence is suggestive of an association of endometriosis with spontaneous miscarriage, preterm birth and small for gestational age babies. A correlation of endometriosis with placenta previa (odds ratio from 1.67 to 15.1 according to various studies) has been demonstrated, possibly linked to the abnormal frequency and amplitude of uterine contractions observed in women affected. Finally, there is no evidence that prophylactic surgery would prevent the negative impact of endometriosis itself on pregnancy outcome. Conclusions Complications of endometriosis during pregnancy are rare and there is no evidence that the disease has a major detrimental effect on pregnancy outcome. Therefore, pregnant women with endometriosis can be reassured on the course of their pregnancies although the physicians should be aware of the potential increased risk of placenta previa. Current evidence does not support any modification of conventional monitoring of pregnancy in patients with endometriosis.

Objective: There is no consensus in current practice guidelines on whether conception by in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) techniques is an indication for performing a fetal echocardiogram. The aim of the study was to assess whether congenital heart defects (CHD) occur more often in pregnancies conceived after IVF/ICSI as compared with those conceived spontaneously. Methods: A systematic search for studies was conducted of PubMed/MEDLINE, EMBASE and Scopus from inception to September 2017. The search included the following medical subject heading (MeSH) terms alone or in different combinations: ‘IVF’, ‘IVF/ICSI’, ‘ART pregnancy’, ‘assisted conception’, ‘birth defect’, ‘congenital heart defects’ and ‘congenital malformation or abnormalities’. Studies comparing neonatal incidence of CHD in pregnancies conceived after IVF/ICSI and those conceived spontaneously were included. Studies reporting on other types of assisted reproductive technology (ART) or lacking information concerning termination of pregnancy were excluded. Chromosomal abnormalities were excluded in all analyzed studies. A meta-analysis of selected cohort studies was conducted to estimate the pooled odds ratio (OR) with 95% CI using a random-effects model. Statistical heterogeneity among the studies was evaluated with the I2 statistic and Q-test. Results: Forty-one studies were identified for review including six case–control and 35 cohort studies. Data of eight selected cohort studies were used for meta-analysis. A total of 25 856 children conceived from IVF/ICSI techniques and 287 995 children conceived spontaneously, involving both singleton and multiple gestations, were included in the analysis. Total CHD events were 337/25 856 (1.30%) and 1952/287 995 (0.68%) in the IVF/ICSI and spontaneous conception groups, respectively. The risk of CHD was significantly increased in the IVF/ICSI group as compared with the spontaneous conception group (pooled OR, 1.45; 95% CI, 1.20–1.76; P = 0.0001; I2 = 44%; P = 0.08). In the subgroup of singleton IVF pregnancies, a significant difference was also obtained (OR, 1.55; 95% CI, 1.21–1.99; P = 0.0005; I2 = 36%; P = 0.18) and also multiple confounding factors adjusted ORs showed statistical significance (pooled OR, 1.29; 95% CI, 1.03–1.60; P = 0.02; I2 = 0%; P = 0.43). Conclusion: Fetuses conceived with IVF/ICSI methods are at an increased risk of developing CHD compared with those conceived spontaneously. However, this finding deserves further investigation due to heterogeneity of both ART procedures and cardiac defects. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Chemotherapy has been associated with premature ovarian failure and infertility in women with cancer. It is well known that anticancer drugs reduce the primordial follicle pool and harm the ovarian blood vascularization leading to ovarian atrophy. However, their mechanism of injury still remains unclear. The aim of this study was to identify the cellular mechanisms involved in the toxicity of chemotherapy drugs belonging to different classes on human ovarian luteinized granulosa cells (LGCs). Treatment with doxorubicin (DXR), paclitaxel (PC), and cisplatin (CP) affected LGCs viability by inducing apoptosis and downregulating both estrogen receptor β and follicle-stimulating hormone receptor in a dose-dependent manner. Several members of the WNT signaling pathway are expressed in granulosa cells where they regulate follicle development, ovulation, and luteinization. Here we show that treatment with DXR, PC, and CP induced upregulation of WNT4 expression, whereas WNT3 expression was downregulated by DXR and PC and upregulated by CP. Analysis of the WNT3 downstream signaling pathway showed that total β-catenin protein levels were reduced upon treatment with DXR and PC. Additionally, restoration of β-catenin signaling by lithium chloride protected LGCs from the injury induced by chemotherapy. The in vitro LGC toxicity model described might represent a tool to identify components of specific signaling pathways, such as the Wnt pathway, that can be targeted in order to limit the follicular damage caused by chemotherapy.

PURPOSE: Gestational trophoblastic neoplasia (GTN) is a rare and aggressive tumour that is usually sensitive to chemotherapy. The usefulness of conventional imaging modalities in evaluating treatment response is limited, mainly due to the difficulty in differentiating between residual tumour tissue and necrosis. The aim of the present study was to evaluate the role of FDG PET or PET/CT in primary staging and in monitoring treatment efficacy. The effect of FDG PET and combined PET/CT on the management of patients with GTN was also evaluated comparing the differences between standard treatments based on conventional imaging and alternative treatments based on PET. METHODS: This retrospective study included 41 patients with GTN referred to San Raffaele Hospital between 2002 and 2010. All patients were studied by either PET or PET/CT in addition to conventional imaging. Of the 41 patients, 38 were evaluated for primary staging of GTN and 3 patients for chemotherapy resistance after first-line chemotherapy performed in other Institutions. To validate the PET data, PET and PET/CT findings were compared with those from conventional imaging, including transvaginal ultrasonography (TV-US) in those with uterine disease, CT and chest plain radiography in those with lung disease and whole-body CT in those with systemic metastases. Conventional imaging was considered positive for the presence of uterine disease and/or metastases when abnormal findings relating to GTN were reported. PET and PET/CT were considered concordant with conventional imaging when metabolic active disease was detected at the sites corresponding to the pathological findings on conventional imaging. In addition, in 12 of the 41 patients showing extrauterine disease, FDG PET/CT was repeated to monitor treatment efficacy, in 8 after normalization of beta human chorionic gonadotropin (?HCG) and in 4 with ?HCG resistance. In some patients, PET or PET/CT findings led to an alternative nonconventional treatment, and this was considered a change in patient management for the study analysis. RESULTS: When compared to TV-US, chest radiography and CT for staging, PET showed a concordance in 91 %, 84 % and 81 % of patients, respectively. In 8 of the 41 patients with extrauterine disease during staging, PET/CT showed a complete response to therapy after ?HCG normalization. PET and PET/CT identified the sites of persistent disease in all seven high-risk patients with ?HCG resistance, of whom four underwent second-line chemotherapy, two surgical removal of resistant disease instead of additional chemotherapy, and one surgical removal of resistant disease and second-line chemotherapy with subsequent negative ?HCG. CONCLUSION: In staging, PET cannot replace conventional imaging and does not show any information in addition to that shown by conventional imaging. The additional value of PET/CT in GTN with respect to conventional imaging is found in patients with high-risk disease. PET can identify the sites of primary and/or metastatic disease in patients with persistent high levels of ?HCG after first-line chemotherapy and may be of additional value in patient management for guiding alternative treatment.

Arteriovenous malformations (AVMs) of the uterus are rare vascular lesions that may be congenital or more commonly acquired after medical or surgical abortion, spontaneous miscarriage, dilation and...